Evolutionary relationship between the bacterial HPr kinase and the ubiquitous PEP-carboxykinase: expanding the P-loop nucleotidyl transferase superfamily

FEBS Lett. 2002 Apr 24;517(1-3):1-6. doi: 10.1016/s0014-5793(02)02518-8.


Similarities between protein three-dimensional structures can reveal evolutionary and functional relationships not apparent from sequence comparison alone. Here we report such a similarity between the metabolic enzymes histidine phosphocarrier protein kinase (HPrK) and phosphoenolpyruvate carboxykinase (PCK), suggesting that they are evolutionarily related. Current structure classifications place PCK and other P-loop containing nucleotidyl-transferases into different folds. Our comparison of both HPrK and PCK to other P-loop containing proteins reveals that all share a common structural motif consisting of an alphabeta segment containing the P-loop flanked by an additional beta-strand that is adjacent in space, but far apart along the sequence. Analysis also shows that HPrK/PCK differ from other P-loop containing structures no more than they differ from each other. We thus suggest that HPrK and PCK should be classified with other P-loop containing proteins, and that all probably share a common ancestor that probably contained a simple P-loop motif with different protein segments being added or lost over the course of evolution. We used the structure-based sequence alignment containing residues specific to HPrK/PCK to identify additional members of this P-loop containing family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Bacteria / enzymology
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Evolution, Molecular*
  • Fungi / enzymology
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleotidyltransferases / chemistry*
  • Nucleotidyltransferases / classification
  • Nucleotidyltransferases / genetics
  • Phosphoenolpyruvate Carboxykinase (ATP) / chemistry*
  • Phosphoenolpyruvate Carboxykinase (ATP) / genetics
  • Protein Conformation
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / chemistry*
  • Protein-Serine-Threonine Kinases / genetics
  • Sequence Homology, Amino Acid


  • Bacterial Proteins
  • HPr kinase
  • Protein-Serine-Threonine Kinases
  • Nucleotidyltransferases
  • Phosphoenolpyruvate Carboxykinase (ATP)